Steroid compounds



United States Patent Oflice Patented June 19, 1956 STEROID COMPOUNDS George Slomp, Jr., Kalamazoo Township, Kalamazoo County, Mich., assignor to The Upjohn Company, Kalamazoo, Mich., a corporation of Michigan No Drawing. Application January 4, 1954, Serial No. 402,127

7 Claims. (Cl. 260-23955) The present invention relates to steroid diepoxy-enolacylates of the pregnane series, and is more particularly concerned with novel 3,20-diacyloxy-5(6),l6(17)-diepoxy-20-pregnene compounds and a novel process for the production thereof.

The novel compounds of the present invention may be represented by the formula:

wherein R1 and R2 are acyl radicals of hydrocarbon carboxylic acids containing up to and including eight carbon atoms.

The process of the present invention consists of treating a 3,20-diacyloxy-5,16,20-pregnatriene with an organic peracid, to obtain selective epoxidation of the 5(6) and the 16(17) double bonds.

It is an object of the present invention to provide 3,20- diacyloxy 5 (6),16(17) diepoxy 20 pregnenes. Another object of the present invention is the selective epoxidation of a 3,20-diacyloxy-5,16,20-pregnatriene to yield 3,20 diacyloxy -5(6),16(17) diepoxy 20 pregnene compounds. Other objects of the present invention will be apparent to those skilled in the art to which this invention pertains.

The diepoxides of this invention are valuable intermediates in the preparation of physiologically active steroid compounds. For example, Reichsteins Compound S acetate and Kendalls Compound F may be obtained from the 3,20-diacyloxy-5(6),16(17)-diepoxy-20- pregnenes by the following steps: hydrolysis to give 3;?- hydroxy 5(6),l6(l7) diepoxypregnan 20 one, bromination to give 3B-hydroxy-5(6),16(17)-diepoxy-21- bromopregnan-ZO-one, treatment with potassium iodide in acetone and treatment of the thus formed 21-iodide with potassium acetate to yield 3,8-hydr0xy-5(6),16(17)-diepoxy-2l-acetoxypregnan-ZO-one, treatment with hydrogen bromide followed by Raney nickel reduction to give 3,8,5a,17a-trihydroXy-Zl-acetoxypregnan-ZO-one and oxidation with chromic acid to give 50,17u-dlhYd1OXY-2lacetoxypregnane-3,20-dione which when boiled with alcoholic potassium carbonate yields 17oc-hydroxy-2l-acetoxy- 4-pregnene-3,20-dione (Compound S acetate). Treat ment of Reichsteins Compound S acetate with Streptomyces fradiae [cf. Colingsworth et al., J. Am. Chem. Soc. 74, 2381 (1952)] yields Kendalls Compound F 1 1/3,l7a,21-trihydroxy-4-pregnene-3,ZO-dione).

The starting compounds of the present invention are the 33,20-diacyloxy-5,16,20-pregnatrienes. These compounds are made from the known 3fi-hydroXy-5,16-pregnadien-ZO-one (16-dehydropregnenolone) or from the 3- esters thereof by esterification and enol esterification. If it is desired to have identical acyloxy groups in the 3- and 20-positions, the esterification and enol esterification may be performed in one step, for example, by heating at reflux or slowly distilling a mixture of 16-dehydropregnenolone with an acid anhydride such as acetic, propionic, butyric, valeric anhydride and the like, or with an isopropenyl ester, such as isopropenyl acetate, propionate, butyrate, valerate, isovalerate, hexanoate, heptanoate, octanoate, benzoate, ,B-cyclopentylpropionate, phenylacetate, toluate, salicylate, and the like, in the presence of an acid catalyst, preferable paratoluenesulfonic acid monohydrate, and isolating the thus-prepared 3fi,20-diacyloxy- 5,16,20-pregnatriene as shown in Preparations 1 and 2. Another method of preparing 3B,20-diacyloxy-5,16,20- pregnatriene consists in enol acylation of lfi-dehydropregnenolone esters as illustrated by the method of Moffett et al., J. Am. Chem. Soc. 74, 2183 (1952), for the preparation of 3,8,20-diacetoXy-5,16,20-pregnatriene. By using a. specific 16-dehydropregnenolone ester, prepared by standard methods of esterification, and subsequent enol acylation, 3 3,20-diacyloxy-5,16,20-pregnatrienes with unlike acyloxy groups can be prepared (cf. Preparations 3 through 6). The esters of 16-dehydropregnenolone are obtained by admixing 16-dehydropregnenolone with an acylating agent such as, for example, ketene, an acid, an acid chloride or bromide or an acid anhydride or other known acylating agents usually in a solvent such as, for example, pyridine, or the like, or an inert solvent, including solvents like benzene, toluene, ether and the like, and heating at a temperature between about zero degrees centigrade and the boiling point of the reaction mixture, usually about room temperature, for a period between about a half hour and about 96 hours. The time of reaction as well as the temperature at which the reaction is carried out, the acylating agent, and the ratio of reactants can be varied. The ester is recovered from the reaction mixture by pouring into ice or cold water, collecting in an appropriate solvent, and washing with successive portions of a mildly basic solution and water to obtain a solution of the product which is essentially neutral. In some instances, the ester crystallizes from the reaction mixture, in which case it is advantageously separated by filtration or other means, washed with water, and thereafter purified by conventional means, such as by recrystallization from a suitable solvent or by chromatographic purification, as deemed necessary.

In carrying out the process of the present invention the selected 3,8,20-diacyloxy-5,16,20-pregnatriene, either as a solid or dissolved in an organic solvent is admixed with the solution of an epoxidizing agent in an organic solvent. Suitable solvents for either the starting compound or the epoxidizing agents are benzene, chloroform, toluene, chlorobenzene, carbon tetrachloride, methylene dichloride, hexane mixtures like Skellysolve B, and the like, with benzene and chloroform preferred. The epoxidizing agents utilized are usually perbenzoic acid, peracetic acid, performic acid, monoperphthalic acid and other available organic peracids. The preferred temperature range for the epoxidation reaction is between zero and thirty degrees centigrade, but a temperature range of minus ten and plus forty degrees centigrade are operative. The time of reaction may vary between a quarter of an hour and twentyfour hours or even longer. The course of reaction and the relative completeness of the reaction, can be followed by iodometric titration of aliquot samples withdrawn from the mixture at regular time intervals. After two moles of peracids are consumed, the reaction can be quenched by adding water or crushed ice. The product, a 3}3,20-di acyloxy a(6 x) ,l6oc(l7oc) diepoxy 20 pregnene is obtained from the organic layer by standard procedures, such as solvent extraction, evaporating the organic solvent and recrystallization from organic solvents such as methanol, ethanol, ethyl acetate and Skellysolve B hexanes, mixtures of these, and the like.

The following examples are illustrative of the process and products of the present invention, but are not to be construed as limiting.

PREPARATION 1 .3 5,20-DIAcEToxY-5, l 6,20-PREGNATRIENE One gram of 35, hydroxy 5,16 pregnadien 20-one (l6-dehydropregnenolone), 100 milligrams of paratoluenesulfonic acid monohydrate, five milliliters of acetic anhydride and five milliliters of benzene were heated under reflux at atmospheric pressure for a period of eight hours. The excess of acetic anhydride, the acetic acid, and the benzene were then removed by distillation under reduced pressure and the reaction mixture was taken up in 100 milliliters of ether. The ether solution was washed three times with twenty milliliter portions of five percent sodium carbonate .solution and subsequently with water until neutral. The ether was then removed under reduced pressure and the residue was recrystallized from acetone to give 35,20-diacetoxy-5,16,20-pregnatriene of melting point 148 to 149 degrees centigrade.

PREPARATION 2.-35,20-DIPRoPIoNYLoxY-5,16,20- PREGNATRIENE A solution of one gram of 35-hydroxy-5,l6-pregnadien- 20-one in twenty-five milliliters of isopropenyl propionate and 150 milligrams of para-toluenesultonic acid monohydrate were slowly distilled for a period of twelve hours. From time to time isopropenyl propionate was added to keep the volume of the solution above ten milliliters. After the mixture had cooled, one gram of sodium bicarbonate was added and the remaining isopropenyl propionate was removed by distillation under reduced pressure. The residue was shaken with ether and ice water, the water layer was extracted with more ether and the combined ether layer was washed with saturated sodium chloride solution, water, and dried over anhydrous sodium sulfate. The ether was removed under reduced pressure and the residue was recrystallized from acetone to yield pure 3 5,20 dipropionyloXy-5 ,16,20-pregnatriene.

In a similar manner by treating l6-dehydropregnenolone with other hydrocarbon carboxylic acid anhydrides or with a selected isopropenyl ester, the following representative esters may be made: 35,20-dibutyryloxy- 5,16,,20 pregnatriene, 35,20 divaleryloxy 5,16,20-pregnatriene, 35,20 di isovaleryloxy 5,16,20 pregnatriene, 35,20-dihexanoyloxy-5,l6,20-pregnatriene, 35,20-diheptanoyloxy 5,16,20 pregnatriene, 35,20 dioctanoyloxy- 5,16,20 pregnatriene, 35,20 dibenzoyloxy 5,16,20- pregnatriene, 35,20 (5' cyclopentylpropionyloxy) 5,16,20 pregnatriene, 35,20 phenylacctoxy 5,16,20- pregnatriene, 35,20 toluyloxy 5,16,20 pregnatriene, 35,20 anisoyloxy 5,16,20 pregnatriene, 35,20 salicyloyloxy 5,16,20 pregnatriene,35,20= gallyloxy- 5,16,20 pregnatriene, 35,20 maleyloxy 5 ,16,20 pregnatriene, 35,20 hemisuccinyloxy 5 ,16,20 pregnatriene, 35,20 dihydrogencitryloxy 5,16,20 pregnatriene, and the like.

PREPARATION 3 .3 5-BENzoYLoxY-5 l 6-PREGNADIEN- 20-oNE PREPARATION 4.-35-EENzoYLoxY-20-AcEToxY-5,16,20-

PREGNATRIENE A solution of 1.0 gram of 35-benzoyloxy-5,l6,-pregnadien-20-one (Preparation 2) and 0.15 gram of paratoluenesulfonic acid monohydrate in twenty milliliters of isopropenyl acetate was slowly distilled for a period of ten hours through a short fractionating column. From time to time isopropenyl acetate was added to keep the volume of the solution above ten milliliters. After cooling the solution remaining in the flask, one gram of sodium bicarbonate was added and the remaining isopropenyl acetate was removed by distillation under reduced pressure at less than thirty degrees centigrade. The residue was shaken with ether and ice water, the water layer was extracted with more ether and the combined ether layer was washed with saturated sodium chloride solution, water, and dried over anhydrous sodium sulfate. The ether was removed under reduced pressure and the residue was recrystallized from methyl alcohol to yield 35-benzoyloxy- 5,16,20-pregnatriene.

PREPARATION 5 .35-vALERYI.oxY-5, 1 6-PREGNADIEN- 20-0NE Following the procedure given in Preparation 3, 35- valeryloxy-S,l6-pregnadien-20-one is prepared by reacting valeryl chloride with 16-dehydropregnenolone at room temperature to produce 35-valeryloxy-5,l6-pregnadien-20- one.

PREPARATION 6.-3 5-vALERYL0xY-20-AcEToxY-5 1 6,20- PREGNATRIENE Following the procedure given in Preparation 4, 35- valeryloxy-ZO-acetoxy-S,l6,20-pregnatriene is produced by heating 35-valeryloxy-5,16-pregnadien-20-one with isopropenyl acetate to yield 35-valeryloxy-20-acetoxy- 5,16,20-pregnatriene.

In the manner as shown by Examples 3 through 6, other representative starting compounds can be prepared such as: 35 phenylacetoxy 20 acetoxy 5,16,20- pregnatriene, 35 toluyloxy 2O acetoxy 5,16,20- pregnatriene, 35 anisoyloxy 20 acetoxy 5,16,20 pregnatriene, 35 salicyloyloxy 20 acetoxy 5,16,20- pregnatriene, 35 propionyloxy 20 acetoxy 5,16,20- pregnatriene, 35 butyryloxy 20 acetoxy 5,16,20- pregna-triene, 35 isovaleryloxy 20 acetoxy 5,16,20- pregnatriene, 35-hexanoyloxy-ZO-acetoxy-S,16,20-pregnatriene, 35-heptanoyloxy-20-acetoxy-5,16,20-pregnatriene, 3 5-0ctanoyloxy-ZO-acetoxy-S,16,20-pregnatriene, 3 5-( 5-cyclopentylpropionyloxy) 20 acetoxy 5,16,20 pregnatriene, 35 ,gallyloxy 20 acetoxy 5,16,20 pregnatriene, 35 maleyloxy 2O acetoxy 5,16,20 pregnatriene, 35 dihydrogencitryloxy 20 acetoxy 5,16,20- pregnatriene, 35 hemisuccinyloxy 20 acetoxy 5 ,16,20- pregnatriene, 35 hemitartaryloxy 20 acetoxy-5,16,20- pregnatriene, 35 acetoxy-20-propionyloxy-S,16,20-pregnatriene, 35-acetoxy-20-butyryloxy-5,16,20-pregnatriene, 35- acetoxy-ZO-valeryloxy-S,16,20-pregnatriene, 35-acetoxy- 20-isovaleryloXy-5,1.6,20-pregnatriene, 35-acetoxy-20-hexanoyloxy-S,16,20-pregnatriene, 35-acetoxy-20-heptanoyloxy 5,16,20 pregnatriene, 35 acetoxy 20 octanoyloxy-S,16,20-pregnatriene, 35-acetoxy 20 benzoyloxy- 5,16,20 pregnatriene, 35 acetoxy 20 phenylacetoxy- 5,16,20-pregnatriene, 35 acetoxy .20 to1uyloxy-5,16,20- pregnatriene, 35-acetoxy-20-anisoyloxy-5,16,20-pregnatriene, 35-acetoxy-20-salicyloyloxy-5,16,20-pregnatriene, 35- acetoxy 20 (5 cyclopentylpropionyloxy) 5,16,20- pregnatriene, 35-acetoxy-20-gallyloxy-5,16,20-pregnatriene, 35 acetoxy 20 maleyloxy 5 ,16,20 pregnatriene, 35 acetoxy 20 dihydrogencitryloxy 5,16,20-pregnatriene, -35 acetoxy 20 hemisuccinylox-y 5,16,20- pregnatriene, 35 acetoxy 20 hemitartaryloxy 5,16,20- pregnatriene, and the like.

Example 1 .--35,20-diacet0xy-5u (6a) ,16a(17a) -diepoxy- ZO-P egn ne A solution containing 0.57 gram (4.12 millimole) of perbenzoic acid in fifteen milliliters of benzene was added to 0.50 gram (1.26 millimole) of 35,20-diacetoxy-5,16,20- pregnatriene. The resulting solution was allowed to stand in the dark for thirty minutes after which period 2.07 molar equivalents of perbenzoic acid had been consumed as determined by titration of an aliquot sample. Titration of a second aliquot sample fifteen minutes later showed no change in peracid concentration. To the reaction mixture was now added ether and cracked ice. The ether phase was separated, washed with cold five percent sodium hydroxide solution and subsequently with water until the wash-water was neutral. The ether solution was then dried over anhydrous sodium sulfate and evaporated at reduced pressure (the ether was distilled below thirty degrees centigrade) to yield a glassy residue. This residue was twice recrystallized to give 35,20-diacetoxy-5a(6a),16ix(17a)diepoxy-20-pregnene or" melting point 162 to 163 degrees centigrade.

Analysis.Calculated for CzsI-IsrOs: C, 69.74; H, 7.96. Found: C, 69.72; H, 8.02.

Example 2. 35,20-dipr0pi0n0xy-5u (6oz) ,16m(170t) diepoxy-ZO-pregnene In the manner given in Example 1, 35,20-dipropionoxy- 5,16,20-pregnatriene is admixed with a solution of perbenzoic acid in benzene to yield 35,20-dipropionoxy-5a- (6a),16a(17a)-diepoxy-20-pregnene.

Example 3.35,20-dibutyryloxy-5a (6a) ,16ot(17oz diep0xy-20-pregnene In the manner given in Example 1, 35,20-dibutyryloxy- 5,16,20-pregnatriene is admixed with 'a solution of perbenzoic acid in benzene to yield 35,20-dibutyryloxy-5u (6a) 16a 17a) -diepoxy-20-pregnene.

' Example 4 .--3 5-benmyloxy-ZO-acetoxy-S a 6 on) ,1 6 a- (17m -diep0xy-20-pregnene In the manner given in Example 1, 35-benzoyloxy-20- acetoxy-5,16,20-pregnatriene is admixed with a solution of perbenzoic acid in benzene to yield 35-benzoyloxy-20- acetoxy-5a(6a),l6a(17a)-diepoxy-20-pregnene.

Example 5 .-3 5-salicyl0yloxy-20-acetoxy-S a 6 a ,1 6 a- (17m) -diepoxy-20-pregnene In the manner given in Example 1, 35-salicyloyloxy- ZO-acetoxy-S,16,20-pregnatriene is admixed with a solution of perbenzoic acid in benzene to yield 35-salicyloyloxy-20-acetoxy-5u(6a),16a( 17oz) -diepoxy-20-pregnene.

Example 6 .-3 5-valeryl0xy-20-acet0xy-5 a (6 a) ,1 6 oz- (1 7a) -diep0xy-20-pregnene In the manner given in Example 1, 35-valeryloxy-20- acetoxy-5,16,20-pregnatriene is admixed with a solution of perbenzoic acid in benzene to yield 35-valeryloxy-20- acetoxy-5a 60c) l 6 x( 17 a) -diepoxy-20-pregnene.

Example 7 .-35-acetoxy-20( 5-cyclop'entylpropionyloxy) -50: (60:) ,160: (17a) -diep0xy-20-pregnene In the manner given in Example 1, 35-acetoxy-20-(5- cyclopentylpropionyloxy) 5,16,20 pregnatriene is admixed with a solution of perbenzoic acid in benzene to yield 3 5-acetoxy-20- 5-cyclopentylpropionyloxy) 5oz 60c) 160c( 17a) -diepoxy-20-pregnene.

Example 8.35,20diacet0xy-5 a (6 a) ,1 6a (1 7a) diepoxy-ZO-pregnene A solution of 3.98 grams of 35,20-diacetoxy-5,16,20- pregnatriene, dissolved in 95 milliliters of chloroform and cooled to five degrees centigrade was admixed with a slurry made of 0.1234 gram of anhydrous sodium acetate and 5.7 milliliters of forty percent peracetic acid. The resulting solution was stored in a refrigerator at five degrees centigrade, and small aliquot samples were removed at regular time intervals for titration. After six hours two molar equivalents of peracetic acid had been consumed. No further change was noted after eighteen additional hours, hence the colorless solution was diluted with chloroform, washed with water, five percent sodium hydroxide solution and then with water until the washwaters were neutral. The chloroform solution was then dried over anhydrous sodium sulfate and evaporated to dryness yielding 3.73 grams of fine needles of 35,20-diacetoxy 5a(6a), 16a(17a) diepoxy 20 pregnene. After-two recrystallizations from methanol the melting point of 3fi,20-dlaC6tOXy-50t(6tx),160t(170t)-dlPOXY-20- pregnene was found to be 166 to 167 degrees centrigrade, [M degrees in chloroform.

Analysis.-Calculated for C25H34Os: C, 69.74; H, 7.96. Found: C, 69.79; H, 8.03.

In a manner similar to Examples 1 through 8 by treating a selected 3 5,20-diacyloxy-5,l6,20-pregnatriene with a peracid such as performic, peracetic, perbenzoic, monoperphthalic acid, and the like, other representative 35,20-diacyloxy 5a(6c),16oc(17ot) diepoxy 20 pregnenes are prepared such as: 35,20-divaleryloxy-5u(6a),16x(17a)- diepoxy 20 pregnene, 35,20 dihexanoyloxy 5:2(600 16u(17a) diepoxy 20 pregnene, 35,20 diheptanoyloxy 5u(6ot),160t(170t) diepoxy 20 pregnene, 35,20- dioctanoyloxy 5oc(6ot),16oz(17a) diepoxy 20 pregnene, 35,20 di (5-cyclopentylpropionyloxy) 5a- (6a),l6o(17u)-diepoxy 20 pregnene, 35,20 dibenzoyloxy 50t(60L),160t(170c) diepoxy 20 pregnene, 35,20 dianisoyloxy 5oz(6ot),16tx(17ot) diepoxy 20- pregnene, 35,20 disalicyloyloxy 5ot(6ot),16oc(l7ot) diepoxy 20 pregnene, 35,20 diphenylacetoxy 50c- (6u),16oc(17ot) diepoxy 20 pregnene, 35 acetoxy- 20 propionyloxy 50t(6ot),16a(17ct) diepoxy 20- pregnene, 35 acetoxy 20 butyryloxy 50t(60t),160c- (17oz) diepoxy 20 pregnene, 35 acetoxy 20- valeryloxy 5ot(6ot),16ot(17ot) diepoxy 20 pregnene, 35 acetoxy 20 isovaleryloxy 5ot(60t),160t(170t)-dlepoxy 20 pregnene, 35 acetoxy 20 hexanoyloxy- 5a(60t),16oc(17et) diepoxy 20 pregnene, 35 acetoxy- 20 heptanoyloxy 5a(6u),l6a(l7a) diepoxy 20- pregnene, 35 acetoxy 2O octanoyloxy 5 x(6a),- 16u(17a) diepoxy 20 pregnene, 35 acetoxy 20- benzoyloxy 5oc(6ot),16zx(17ot) diepoxy 20 pregnene, 35 acetoxy 20 phenylacetoxy 50c(60t),l60t(l7ot) diepoxy 20 pregnene, 35 acetoxy 20 toluyloxy- 5ot(6oc),16oc(17ot) diepoxy 20 pregnene, 35 acetoxy- 20 anisoyloxy 5ot(6oc),16oc(17oc) diepoxy 20 pregnene, 35 acetoxy 20 salicyloyloxy 5u(6a),16a- (17a) diepoxy 2O pregnene, 35 acetoxy 20- gallyloxy 50z(6ot),16ot(17oc) diepoxy 20 pregnene, 35 acetoxy 20 maleyloxy 5ot(6ot),16oc(l7ot) diepoxy 20 pregnene, 35 acetoxy 20 dihydrogencitryloxy 50t(60L),160L(1706) diepoxy 20 pregnene, 35 acetoxy 20 hemisuccinyloxy 5ot(6ot),16oc(17ot)- diepoxy 20 pregnene, 35 acetoxy 20 hemitartaryloxy 5oc(6oc),16ot(17ot) diepoxy 20 pregnene, 35- phenylacetoxy 20 acetoxy 5a(6a),16u(17a) diepoxy 20 pregnene, 35 toluyloxy 20 acetoxy 5ot(6zx),16oc(l7ot) diepoxy 20 pregnene, 35- anisoyloxy 20 acetoxy 5oc(6u),16oc(17oc) diepoxy- 20 pregnene, 35 propionyloxy 20 acetoxy 5a- (60c),16ot(17oc) diepoxy 20 pregnene, 35 butyryloxy 20 acetoxy 5oc(6ot),16ot(l7a) diepoxy 20- pregnene, 35 isovaleryloxy 20 acetoxy 5oz( 6a),16 x- (17oz) diepoxy 20 pregnene, 35 hexanoyloxy 20- acetoxy 5ot(6ot),16ot(l7a) diepoxy 20 pregnene, 35 heptanoyloxy 20 acetoxy 5u(6ot),16a(17a) diepoxy 20 pregnene, 35 octanoyloxy 20 acetoxy- 5ot(6ot),l6ot(17oc) diepoxy 20 pregnene, 35 (5- cyclopentylpropionyloxy) 20 acetoxy 5oc(60t),160c- (17a) diepoxy 20 pregnene, 35 gallyloxy 20- acetoxy 5ot(6a),16ot(17ot) diepoxy 20 pregnene, 35 maleyloxy 20 acetoxy 5ot(6a),l6o(17ot) diepoxy 20 pregnene, 35 dihydrogencitryloxy 20- acetoxy 5a(6a),16a(17 x) diepoxy 20 pregnene, 35 hemisuccinyloxy 20 acetoxy 5a(6a),16a(17a)- diepoxy 20 pregnene, 35 hemitartaryloxy 20- 7 cetoxy x(1 a) poxy 20 pr ene an the like.

It is to be understood that this invention is not to be limited to the exact details of operation or exact compounds shown and described as obvious modifications and equivalents will be apparent to one skilled in the art and the invention is therefore to be limited only by the scope of the appended claims.

I claim:

1. A 3fi,20-diacyloXy-5a(61;),164417a) diepoxy-ZO- pregnene of the formula:

wherein R1 and R2 are the acyl radicals of hydrocarbon carboxylic acids containing up to and including eight carbon atoms.

2. 3/3,20-diacetoxy-5a(6a),16a(17a)-diepoxy-20-pregnene.

3. 3 5,20-dipropionyloxy-5 a(6a) ,16 x( 175x) -diepoxy-20- pregnene.

4. 3B be-nzoyloxy 20 acetoxy 5oc(6oc),16oc( l7a')-diepoxy-ZO-pregnene.

5. 3 p-acetoxy-20-( B-cyclopentylpropionyloxy) -5 a(6a) l6oc( 17cc -diepoxy-20-pregnene.

6. A process for the production of a 3,8,20-diacyloxy- 5a(6et),l6u(17a)-diepoxy-20-pregnene which comprises 8 mixing a 35,20-diacyloxy-5,16,20-pregnatriene of the formula:

References Cited in the file of this patent 30 UNITED STATES PATENTS 2,312,344 Logemann Mar. 2, 1943 2,323,277 Miescher June 29, 1943 2,602,769 Murray July 8, 1952 2,686,181 Julian Aug. 10, 1954 35 OTHER REFERENCES Mofiet: JACS, 74, pp. 2183-785 1952 

1. A 3B, 20-DIACYLOXY-5A(6A),16A(17A) - DI - EPOXY-20PREGNENE OF THE FORMULA 